The enzyme guanylate cyclase forms cyclic GMP from GTP. It occurs in high activity in lung in two forms, soluble and insoluble. We have been studying the biochemical mechanisms by which the enzyme is activated. The activity of the soluble enzyme can be increased four-fold by an oxygen-dependent reaction, which we believe involves the oxidation of unsaturated fatty acids. A much greater activation can be achieved by nitrosocompounds, such as sodium nitroprusside. This reaction does not require oxygen. It has not been possible to chemically describe the mechanism for the oxidative activation of guanylate cyclase with the relatively impure preparations available. We are attempting to purify the enzyme from bovine lung, in order to accomplish this description.